Contrary to a widely-held assumption about heterosexual transmission of HIV, the normal mucosal lining of the female genital tract is not a foolproof barrier to viral penetration, scientists at the Northwestern University School of Medicine in Chicago report at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San Francisco.
"This is an unexpected and important result," says Thomas Hope of Northwestern, "because it is generally believed that the squamous epithelium of the female genital tract is an efficient barrier to viral penetration."
By labeling individual HIV virons with photoactivated fluorescent tags, Hope and his Northwestern colleagues were able to view the virus as it penetrated the squamous epithelium, the outermost most lining of the female genital tract.
The studies were conducted with lab cultures of human tissue obtained during hysterectomies and in tissue from rhesus macaque monkeys.
The researchers determined that HIV penetrated the genital skin barrier primarily by moving quickly, in just four hours, between skin cells to reach 50 microns beneath the skin, the depths in the tissue at which the immune cells targeted by HIV are located.
HIV penetration was more common in the outermost superficial squamous epithelial layers and likely occurred during the normal turnover and shedding of skin cells. Then the skin cells are no longer tightly bound together, so water and HIV can easily enter.
Until now, scientists have had minimal data about how the virus penetrates epithelial barriers to find its specific immune cell targets such as CD4 positive T cells, macrophages, Langerhans cells, and dendritic cells.
Hope points out that new therapeutics or prevention strategies to block the entry of HIV through the superficial layers protecting the female genital tract are urgently needed.
The latest data from the U.S. Centers for Disease Control show that 31 percent of total new HIV infections each year can be traced to high-risk heterosexual contact.
For more information:
Contact John Fleischman, ASCB science writer, jfleischman@ascb.org, (513) 929-4635, (513) 706-0212,
or
Cathy Yarbrough, freelance ASCB annual meeting media coordinator, cyarbrough@ascb.org, (858) 243-1814.
or
Thomas Hope
Department of Cell and Molecular Biology
Northwestern University Medical School
Chicago, IL 60611
thope@northwestern.edu
(312) 503-1360
Author presents his paper, "Analysis of the Interaction of HIV with Female Genital Tract Tissue as a Model to Understand Sexual Transmission," on Tuesday, Dec.16 at 3:45 p.m., during Minisymposium 20, Cellular Response to Infectious Agents, in Room 104, Moscone Center
Authors: A. Trull, S. McCoombe, M. McRaven, Northwestern University Medical School, Chicago, IL; R.S. Veazey, Tulane University, New Orleans, LA; T. Hope, Northwestern University Medical School.